The term “appendages” according to the invention encompasses the assemblage of keratinic appendices exhibited on the body surface, in particular the hair, eyelashes, eyebrows, nails, and hair.
The skin is a vital organ that covers the entire surface of the body and provides protective, sensitive, immune, metabolic, or even thermoregulatory functions. The skin, like other organs, is subject to aging. So, one of the major mechanisms implicated in the processes of aging is the accumulation of oxidative damage in essential molecules such as membrane lipids, proteins, DNA, and most particularly mitochondrial DNA (DNAmt).
Oxidative damage is caused by free radicals, chemically unstable and very reactive species generated by intracellular metabolism or external aggressions. Among these external aggressions, the following may be cited: UV radiation, toxins, atmospheric pollutants, and alimentary oxidants. Premature aging is observed in the skin, occurring in areas exposed to radiation, characterized by phenomena of alterations in the macromolecules (lipid peroxidation, carbonylation of proteins) affecting, in particular, elastin, collagen, and fibronectin. Progressive decline with age can also be shown in the mitochondrial functions with age, probably linked to the accumulation of mutations on DNAmt (K. Singh (2004), Ann. NY Acad. Sci., 1019).
One of the important consequences of the accumulation of oxidative damage is the reduction in the capacity of the cell to produce ATP (Porteous et al. (1998), Eur. J. Biochem. 257(1), 192-201). Thus, the phenomenon of cellular aging is in proportion to oxidative damage which the cell undergoes as well as to the process of producing the energy the cell needs to survive.
The body possesses defense mechanisms capable of trapping or of transforming free radicals (enzymes, glutathione, vitamins A and E, coenzyme Q10, etc.). However, these antioxidant defense systems often prove to be insufficient under the numerous stresses and external aggressions to which the body, and the skin in particular, are subjected.
In this context, the particular properties of cytochrome C appear to be particularly interesting.
Cytochrome C is a small soluble protein, 15 KDa atomic mass, which plays an essential role in mitochondrial function and in cellular survival. Cytochrome C is a molecule retained to a high degree in the majority of the eucaryotes; it is found in the mitochondria of plants, animals, and numerous single-celled organisms. Cytochrome C exhibits a proteinic structure organized around a porphyrin made up of four pyrrole nuclei, themselves linked to an iron atom.
The principal role of cytochrome C is to provide for the transfer of electrons, due to a change in the valence of the iron atom. Cytochrome C, which is soluble, thus transports the electrons from a III coordination compound (coenzyme QH2/cytochrome C reductase) to a IV coordination compound (cytochrome oxidase). The electrons, which are the substrate of cytochrome oxidase, are then transferred by the enzyme to the oxygen.
The search for compounds capable of stimulating the mitochondria and raising the cellular energy level in order to prevent or to combat signs of cutaneous aging or damage caused by external aggressions, such as UV rays, radiation, or exposure to toxins or to pollutants, is an important concern of medical research and of cosmetics. In this regard, solutions have been proposed such as intake of substances implicated in energy metabolism, and more particularly, intermediaries or cofactors of the Krebs cycle such as fumarate, L-malate, acetyl CoA (WO 02064129), or even treating the skin with substances capable of reducing the free radicals, such as vitamin C (US 2004/0086526) or L-ergothionine (WO 9836748). But to the knowledge of the applicant, no cosmetic or pharmaceutical composition including polypeptides or peptides capable of activating cytochrome C has yet been described.